Fibronectin is a high molecular weight glycoprotein found in extracellular fluids and connective tissue and associated with basement membranes. In cell culture, fibronectin is present in cell layers of substrate attached cells and is organized into an extracellular fibrillar matrix. Collagen, a second component of the matrix, binds to fibronectin and can be cross-linked to fibronectin by plasma transglutaminase. Other molecules, including sulfated proteoglycans, fibrin, gangliosides, and components of bacteria cell walls, also interact with fibronectin. As a result of these multiple interactions, fibronectin probably functions as an adhesive protein and opsonin. A variety of biochemical, immunological, and cell biological techniques will be used to further describe the structure and function of fibronectin. Experiments will be directed towards (1) further characterizing a 27 kd fragment of fibronectin which can be cross-linked to collagen and fibrin and which binds to bacteria; (2) quantitating the extent of transglutaminase-catalyzed cross-linking between fibronectin and collagen in cell structure and in proliferating tissues; (3) comparing fibronectin to other substrates of plasma transglutaminase; (4) describing the isotherms for binding of fibronectin to various types and forms of collagen, to fibrinogen and fibrin, to bacteria, and to platelets; (5) discovering the determinants of collagen, fibrin, and bacterial cell walls which are important for binding and cross-linking of fibronectin; (6) learning if and how fibronectins from different tissues differ from one another; (7) studying how fibronectin-fibrin cross-linking influences cells which are cultured in fibrin clots; and (8) comparing the cell-binding and collagen-binding activities of fibronectin to comparable activities of von Willebrand factor.